Hepatitis C caused by HCV is one of the world's most widely spread liver diseases. According to the annual reports of the World Health Organization (WHO), more than 130-150 mln people are infected with HCV and more than 700 thousand individuals die from HCV [WHO. Hepatitis C. WHO fact sheet No 164. Updated July 2016, http://www.who.int/mediacentre/factsheets/fs164/en/]. HCV demonstrates a high genetic diversity and is characterized by regional variations of (gT) HCV genotypes. Genotype 1 (gT1) is the most common in the world (83.4 mln people, or 46.2% of all HCV-infected; about one third of them are in East Asia). Genotype 3 (gT3) is the second most common genotype. Globally, 54.3 mln people (30.1%) are infected with gT3. Genotypes 2, 4, and 6 account for 22.8% of all HCV-infected people, while genotype 5 (gT5) accounts for <1%. While genotypes 1 and 3 prevail in the majority of countries regardless of their economic status, the greatest occurrence of genotypes 4 and 5 are in low-income states [Messina, J. P. at al. Global Distribution and Prevalence of Hepatitis C Virus Genotypes. Hepatology 2015, 61(1), 77-87.] Hepatitis C caused by HCV is one of the world's most widely spread liver diseases. According to the annual reports of the World Health Organization (WHO), more than 130-150 mln people are infected with HCV and more than 700 thousand individuals die from HCV [WHO. Hepatitis C. WHO fact sheet No 164. Updated July 2016, http://www.who.int/mediacentre/factsheets/fs164/en/]. HCV demonstrates a high genetic diversity and is characterized by regional variations of (gT) HCV genotypes. Genotype 1 (gT1) is the most common in the world (83.4 mln people, or 46.2% of all HCV-infected; about one third of them are in East Asia). Genotype 3 (gT3) is the second most common genotype. Globally, 54.3 mln people (30.1%) are infected with gT3. Genotypes 2, 4, and 6 account for 22.8% of all HCV-infected people, while genotype 5 (gT5) accounts for <1%. While genotypes 1 and 3 prevail in the majority of countries regardless of their economic status, the greatest occurrence of genotypes 4 and 5 are in low-income states [Messina, J. P. at al. Global Distribution and Prevalence of Hepatitis C Virus Genotypes. Hepatology 2015, 61(1), 77-87.].
Considerable progress in the therapy of hepatitis C that has been achieved in recent years is primarily associated with the discovery of Sofosbuvir (Sovaldi®, PSI-7977, GS-7977), which is a nucleoside prodrug of an HCV NS5B inhibitor and an Sp isomer of prodrug PSI-7851 [Sofia, M. J. et al. Discovery of a β-D-20-Deoxy-20-rfluoro-2 0-β-C-methyluridine Sovaldi Nucleotide Prodrug (PSI-7977) for the Treatment of Hepatitis C Virus. J. Med. Chem. 2010, 53, 7202-7218. Sofia, M. J. et al. Nucleoside phosphoramidate prodrugs. U.S. Pat. No. 7,964,580 (2011), U.S. Pat. No. 8,334,270 (2012). Patent RU 2478104 (2013)],

Sovaldi® is now widely applied in the combination therapy of hepatitis C, including together with HCV NS5A inhibitors. Sovaldi® has become the first nucleotide approved by FDA and EC regulating agencies for the combination therapy of patients with hepatitis C infected with various HCV genotypes (gT). In clinical studies, it has shown high potency against six HCV genotypes (gT1-gT6) [I. M. Jacobson et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. Engl. J. Med. 2013, 368, 1867-1877. E. Lewirz et al. Sofosbuvir for previously untreated chronic hepatitis C infection. Engl. J. Med. 2013, 368, 1878-1887].
PSI-7851 and its stereoisomers PSI-7976 and PSI-7977 metabolize into triphosphate PSI-7409, which actually is an HCV NS5B polymerase inhibitor [E. Murakami et al. Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J. Biol. Chem. 2010, 285(45), 34337-34347],

There are other known Sovaldi® analogs [U.S. Pat. No. 8,334,270 (2012). M. J. Sofia et al. Discovery of a β-D-20-Deoxy-20-r-fluoro-20-β-C-methyluridine Nucleotide Prodrug (PSI-7977) for the Treatment of Hepatitis C Virus. J. Med. Chem. 2010, 53, 7202-7218.] including cyclohexyl (S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydrofuran-2-ylmethoxy]-phenoxy-phosphorylamino}-propionate of formula A1, just like PSI-7851 and its phosphor stereoisomers PSI-7976 and PSI-7977 (Sovaldi®), metabolize into triphosphate PSI-7409,

However, despite recent progress in the therapy of hepatitis C, a quest for novel prodrugs of an HCV NS5B inhibitor with improved characteristics remains a major challenge.